Accurate early diagnosis is very important in Alzheimer 's Disease, now that potential treatments are available. In an earlier study, (Archives of General Psychiatry 1992, 49:402-408), we compared 26 patients with moderately severe AD to 16 normal subjects using SPECT assessment of regional cerebral blood flow (rCBF). SPECT abnormalities were detected, with best diagnostic discrimination provided by temporoparietal cortex, an area known to be severely affected neuropathologicalty. In the current study, we wished to examine patients with very early AD at point of contact to see if similar changes are found to those seen in more advanced cases. We assessed 23 minimally impaired elderly patients at-risk for AD (mean Mini-Mental State score 23+4) and 12 controls. We revealed significant changes in SPECT rCBF in temporal neocortex, parietal cortex, mesial temporal regions and portions of prefrontal and cingulate cortex on SPM analysis. This is the first report of mesial temporal bloodflow change in AD. Findings are also consistent with the argument that as in HD, pathological changes in AD may potentially be detectable not only very early in the course of the disease, but years before clinical disease onset. This hypothesis is reinforced by recent studies by Priman (1996) and Small (1995).